EU Committee Recommends Orphan Drug Status for Ziopharm’s IL-12 Gene Therapy for Glioblastoma

A European Medicines Agency (EMA) committee has recommended orphan drug designation for Ziopharm Oncology‘s interleukin (IL)-12 gene therapy — known as the Controlled IL-12 platform — for the treatment of glioblastoma, a very aggressive type of brain cancer.

The European Commission will now decide whether or not to grant the designation to the investigational therapy based on this positive opinion from the EMA’s Committee for Orphan Medicinal Products (COMP).

Orphan medicinal product designation is given to new medicines that have the potential to be a safe and effective treatment for life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union and with no approved treatments.

This status is expected to provide regulatory support and financial benefits, to accelerate the clinical development and review of the Controlled IL-12 platform, and to ensure a 10-year period of marketing exclusivity in the EU upon regulatory approval.

The U.S. Food and Drug Administration gave the Controlled IL-12 platform orphan drug designation in 2015 and fast track designation (which is also designed to facilitate the medicine’s development and review process) earlier this year for the treatment of glioblastomas.

The controlled IL-12 platform, or Ad-RTS-hIL-12 plus veledimex, is a new gene therapy intended to control the production of IL-12, a molecule that triggers the activation and expansion of immune T-cells, boosting anti-cancer immune responses.

First, a gene with the instructions to produce the IL-12 protein is delivered through a modified and safe version of a virus directly to tumor sites. Patients are then given a capsule of veledimex, which triggers the production of IL-12 from the implanted gene to varying degrees, depending on dosage.

COMP’s positive opinion is based on results from a Phase 1 dose-escalation trial (NCT02026271) evaluating the safety, tolerability, and efficacy of the Controlled IL-12 platform in patients with recurrent glioblastoma.

Glioblastoma is the most common and deadliest type of brain cancer, with fewer than 5% of patients living more than five years after their diagnosis. When this cancer returns, a patient’s median overall survival is six to nine months. With few therapeutic options, there is an urgent and unmet need to develop efficient therapies against this type of cancer.

The trial’s preliminary results showed that treatment with the Controlled IL-12 platform (with 20 mg of veledimex a day) prolonged patients’ overall survival to a median of 12.7 months. In a subset of these patients who received low-dose steroids, the median overall survival reached 17.8 months, compared with 6.4 months for patients receiving high-dose steroids for the same period.

Regarding safety, all adverse events were manageable and reversible.

Ziopharm announced earlier this year the completion of enrollment in an expansion substudy (NCT03679754) that increased the number of recurrent glioblastoma patients treated with the Controlled IL-12 platform from 15 (in the Phase 1 trial) to up to 51. In the additional group of patients, 75% (27 of 36) received low-dose steroids.

Results of both studies are expected to be published in a scientific journal or shared in medical meetings this year.

“We are pleased to receive a positive opinion from EMA COMP for orphan drug designation, as this represents another important milestone for our clinical program to treat recurrent glioblastoma,” Laurence Cooper, Ziopharm’s CEO, said in a press release.

The company is also conducting Phase 1 studies evaluating the Controlled IL-12 platform in pediatric patients with brain tumors (NCT03330197) and in combination with Opdivo (nivolumab) — an approved treatment for other types of cancer — in adults with relapsed glioblastoma (NCT03636477).